APOBEC (“apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like”) is a family of evolutionary conserved proteins. Members of this family are C-to-U editing enzymes involving a distinctive zinc-finger catalytic domain. Some APOBEC proteins are made up of a single zinc-finger domain while others have two, referred to N- and C-terminal domains. The carboxy-terminal domain is functional for all but APOBEC3DE. The N-terminal domains of APOBEC3B, APOBEC3DE, APOBEC3F and APOBEC3G are non-functional. More specifically, the zinc finger cytidine deaminase domain and is essential for cytidine deamination.
U.S. patent application 2009/0260090 provides methods for preventing the occurrence or progression of a cancer or pre-cancer conditions associated with expression, or overexpression of APOBEC3 proteins.
Physiologically, expression of APOBEC3A is particularly well detected in cells of myeloid lineage and this is positively regulated by INF-α (Berger et al., 2011; Koning et al., 2009; Refsland et al., 2010).
However the true physiological functions of APOBEC3 proteins are not yet conclusively established.
Recently published data indicate that APOBEC3A is a particular deaminase which acts by equally efficient deamination of cytosine and 5-methylcytosine to uracil and methyluracil (thymidine) in single-stranded DNA (ssDNA) (Suspene et al., 2011; Wijesinghe and Bhagwat, 2012). Consequently APOBEC3A can trigger genetic and epigenetic modifications in extensively dividing cells. Uracil excision followed by abasic endonuclease cleavage of the DNA strand, leads to double strand breaks (DSBs) (Landry et al., 2011). DNA breaks are a potent signal for the initiation of DNA damage response leading to cell-cycle checkpoints. Failure to repair a single DSB prior to cell division may lead to prolonged cell cycle arrest, failure to undergo cell division and ultimately cell death. Cells that escape arrest and continue to divide with unrepaired breaks may eventually succumb to mitotic catastrophe (Hiom, 2010).